Differential survival following trastuzumab treatment based on quantitative HER2 expression and HER2 homodimers in a clinic-based cohort of patients with metastatic breast cancer
1 Faculty of Medicine, Kyoto University, Kyoto, Japan
2 Department of Research and Development, Monogram Biosciences, Inc., South San Francisco, CA, USA
3 Department of Clinical Research, Monogram Biosciences, Inc, South San Francisco, CA, USA
4 Division of Clinical Trials and Research and Department of Surgery, Tokyo Metropolitan Cancer and Infectious Disease Center, Komagome Hospital, Tokyo, Japan
5 Division of Breast Oncology, National Kyushu Cancer Center, Fukuoka, Japan
6 Breast Surgical Oncology, St Luke's International Hospital, Tokyo, Japan
7 Department of Breast Oncology, Aichi Cancer Center Hospital, Aichi, Japan
8 Department of Surgery, National Hospital Organization, Osaka National Hospital, Osaka, Japan
9 Department of Breast Oncology, National Hospital Organization, Shikoku Cancer Center, Matsuyama, Japan
10 Department of Biostatistics and Epidemiology, Yokohama City University Medical Center, Yokohama, Japan
BMC Cancer 2010, 10:56 doi:10.1186/1471-2407-10-56Published: 23 February 2010
We have recently described the correlation between quantitative measures of HER2 expression or HER2 homodimers by the HERmark assay and objective response (RR), time-to progression (TTP), and overall survival (OS) in an expanded access cohort of trastuzumab-treated HER2-positive patients with metastatic breast cancer (MBC) who were stringently selected by fluorescence in situ hybridization (FISH). Multivariate analyses suggested a continuum of HER2 expression that correlated with outcome following trastuzumab. Here we investigate the relationship between HER2 expression or HER2 homodimers and OS in a clinic-based population of patients with MBC selected primarily by IHC.
HERmark, a proximity-based assay designed to detect and quantitate protein expression and dimerization in formalin-fixed paraffin-embedded (FFPE) tissues, was used to measure HER2 expression and HER2 homodimers in FFPE samples from patients with MBC. Assay results were correlated with OS using univariate Kaplan-Meier, hazard function plots, and multivariate Cox regression analyses.
Initial analyses revealed a parabolic relationship between continuous measures of HER2 expression and risk of death, suggesting that the assumption of linearity for the HER2 expression measurements may be inappropriate in subsequent multivariate analyses. Cox regression analyses using the categorized variable of HER2 expression level demonstrated that higher HER2 levels predicted better survival outcomes following trastuzumab treatment in the high HER2-expressing group.
These data suggest that the quantitative amount of HER2 expression measured by Hermark may be a new useful marker to identify a more relevant target population for trastuzumab treatment in patients with MBC.